Standard-dose Versus High-dose Flu Vaccine in Solid Organ Transplant.

• Sponsor: Inova Health Care Services (Other)
• Overall Status: Completed
• CT.gov ID: NCT01808456
• Collaborator: (none)
• Enrollment: 62
• Location: 1
• Arms: 2
• Duration (Months): 38
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

Influenza infection in recipients of solid organ transplants recipients while on maintenance immunosuppressant therapy is associated with increased morbidity and mortality. Although influenza vaccination is recommended in these high-risk patients, safety and immunogenicity of commercially available different strengths of influenza vaccine have not been established.

The primary study objective is to determine the safety and immunogenicity of Fluzone and Fluzone High-Dose, with a secondary objective to determine the tolerability and efficacy of two different strengths of trivalent influenza vaccine (TIV, flu vaccine). Both vaccines are commercially available for use in the general population. Fluzone is approved for use in 6 months of age and older, and Fluzone High-Dose is approved for use in 65 years of age and older.

This is an exploratory, open-label, parallel group, observer blinded, prospective study. All recipients of kidney, lung, heart transplants who attend for post-transplant follow-up, at least 30-days after transplantation at Inova Fairfax Hospital Transplant Center will be eligible for enrollment.

Enrolled patients will be followed for three months (a total of 4 visits) following enrollment and randomization: day 0 (enrollment) and follow-up visits at weeks 1, 4, 8, and 12.

Condition or Disease	Intervention/Treatment	Phase
Influenza, Human; Transplantation Infection	Biological: influenza trivalent inactive vaccine; Biological: influenza trivalent inactive vaccine high dose	Phase 4

Detailed Description

A potential strategy to enhance immune responses to influenza vaccine in this patient population could be to use different strengths of TIV. One of the pathways that can improve the immunogenicity of inactivated vaccines is to increase the dose of influenza antigens contained in the vaccine. Studies have demonstrated that increasing the dose of the influenza virus hemagglutinin for each of the commonly encountered viral strains beyond the conventional dose of 15 microgram for each strain is associated with dose-dependent increase in serum antibody titers.

Influenza TIV is commercially available in two different strengths, Fluzone as well as Fluzone High-Dose, and it is valuable because of variable immunogenic potency of different strengths. Fluzone is approved for use in persons 6 months of age and older. High-dose Fluzone is approved for use in persons 65 years of age and older.

The purpose of this exploratory study is to assess the safety, tolerability, and immunogenicity of these two commercially available different strengths of TIV in solid organ transplant recipients (kidney, heart and lung) in the period after 30 days after transplant procedure. We will evaluate the safety, tolerability (reactogenicity) and immunogenicity of two different strengths of commercially available TIV in a single center, cluster randomization, investigator blinded, study by enrolling patients in the post-transplant clinic at Inova Fairfax Hospital from: August 1, 2013 - March 31, 2014; and August 1, 2014 to March 31, 2015.

Study protocol will remain active till December 31, 2016. All bio-specimens will be stored till December 31, 2016.

Study Design

• Study Type: Interventional
• Actual Enrollment: 62 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: Phase IV, Pilot, Randomized, Investigator-blinded, Study to Evaluate the Reactogenicity and Immunogenicity of Standard-dose Versus High-dose Inactivated Influenza Vaccine After Kidney, Heart and Lung Transplantation.
• Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: High Dose Flu Vaccine influenza trivalent inactive vaccine high dose. IM (intramuscular) injection one time administration	Biological: influenza trivalent inactive vaccine high dose; one time IM injection of high dose influenza vaccine to measure immunogenicity, safety, and efficacy in organ transplant recipients; Other Names: Fluzone High Dose (R)
Active Comparator: Flu Vaccine influenza trivalent inactive vaccine IM injection one time administration	Biological: influenza trivalent inactive vaccine; one time IM injection of standard influenza vaccine to measure immunogenicity, safety, and efficacy in organ transplant recipients; Other Names: Fluzone(R) flu vaccine

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Local Site Reactions [Day 1 and weeks 1, 4, and 12]

   Evaluation of local and systemic reactions, use of analgesics or antipyretics.

2. Measurement of Strain-specific Hemagglutination Inhibition (HI) Antibody Titers [Week 1, 4, and 12]

   Number of patients and percentage of subjects achieving hemagglutination inhibition (HI) titer≥40

Secondary Outcome Measures

1. All Cause ED Visits/Unscheduled Clinic Visits [day 1 - 3 months]

   All-cause outpatient/Emergency department visits during study follow-up (other than pre-specified post transplant follow-up visits).

2. Number and Percentage of Subjects in Each Group Achieving Seroconversion for Each Strain [Week 4 and Week 12]

   Number and percentage of subjects in each group achieving seroconversion (at least 4-fold increase in titers from baseline) for each any strain at weeks 4 and 12

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. All adults age ≥18 years of age following solid organ transplants (kidney, heart and lung) of all races and gender unless as specified in the exclusion criteria.

2. At least 30 days after organ transplantation of kidney, heart, or lung.

3. In good health as determined by a) medical history, b) physical examinations, c) clinical judgment of the investigator team.

4. Informed consent will be obtained from all the subjects before enrollment into the study, after the nature of the study has been fully explained to the satisfaction of the participant.

5. Non-English speaking persons will be included ONLY if consent can be obtained with the help of the translator or interpreter.

Exclusion Criteria:

1. Less than 30 days after transplantation procedure.

2. Post operative complications of any type.

3. Transplant organ dysfunction and/or under evaluation for possible infection.

4. Recent acute transplant rejection and treatment for rejection for the past 30 days.

5. Receiving another investigational drug or biologic for transplant.

6. Previous history of allergic reaction to influenza vaccine, chicken egg or other unknown allergic reactions to flu vaccine or other vaccines.

7. Acute ongoing respiratory illness.

8. Bleeding diathesis or on anticoagulation therapy.

9. Major surgery (pre-arranged) planned during the study period.

10. Any condition that may preclude the participant from completion of study related activities; such as planned travel, or out of the state of residence and not able to return for follow-up visits or relocation of residence.

11. Females of reproductive age unless proven to be urine HCG negative at the time of participation.

12. Recent opportunistic infection, such as CMV, EBV, BK viral reactivation, or any other documented or laboratory confirmed opportunistic infection or on treatment for confirmed infection.

13. Vulnerable subjects such as aged less than 18 years, pregnant women, nursing home residents or other institutionalized persons, students, employees, prisoners, and persons who may not be able to make independent decisions or is considered to have a cognitive impairment, or non-English speaking in the absence of a reliable interpreter or translator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Inova Fairfax Hospital	Falls Church	Virginia	United States	22042

Sponsors and Collaborators

• Inova Health Care Services

Investigators

• Principal Investigator: Ravinder Wali, MD, Inova Fairfax Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Inova Health Care Services
• ClinicalTrials.gov Identifier: NCT01808456
• Other Study ID Numbers: IFH20132015
• First Posted: Mar 11, 2013
• Last Update Posted: Jul 22, 2022
• Last Verified: Jul 1, 2022

• Keywords provided by Inova Health Care Services: kidney transplant; heart transplant; lung transplant; influenza vaccine
• Additional relevant MeSH terms: Influenza, Human; Vaccines

Study Results

Participant Flow

Arm/Group Title	SD-IIV3	HD-IIV3
Arm/Group Description	Standard-dose trivalent (SD-IIV3) flu vaccine	high dose trivalent flu vaccine recipients
Period Title: Overall Study
STARTED	30	32
COMPLETED	26	30
NOT COMPLETED	4	2

Baseline Characteristics

Arm/Group Title	SD-IIV3	HD-IIV3	Total
Arm/Group Description	Standard-dose trivalent (SD-IIV3) seasonal influenza vaccine	high-dose trivalent (HD-IIV3) seasonal influenza vaccine	Total of all reporting groups
Overall Participants	30	32	62
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	27 90%	26 81.3%	53 85.5%
>=65 years	3 10%	6 18.8%	9 14.5%
Age (years) [Mean (Inter-Quartile Range) ]
Mean (Inter-Quartile Range) [years]	54.9	56.6	55.7
Sex: Female, Male (Count of Participants)
Female	7 23.3%	13 40.6%	20 32.3%
Male	23 76.7%	19 59.4%	42 67.7%
Region of Enrollment (Count of Participants)
United States	30 100%	32 100%	62 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Local Site Reactions
Description	Evaluation of local and systemic reactions, use of analgesics or antipyretics.
Time Frame	Day 1 and weeks 1, 4, and 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High Dose Flu Vaccine	Flu Vaccine
Arm/Group Description	influenza trivalent inactive vaccine high dose. IM (intramuscular) injection one time administration influenza trivalent inactive vaccine high dose: one time IM injection of high dose influenza vaccine to measure immunogenicity, safety, and efficacy in organ transplant recipients	influenza trivalent inactive vaccine IM injection one time administration influenza trivalent inactive vaccine: one time IM injection of standard influenza vaccine to measure immunogenicity, safety, and efficacy in organ transplant recipients
Measure Participants	32	30
Count of Participants [Participants]	2 6.7%	2 6.3%

2. Primary Outcome

Title	Measurement of Strain-specific Hemagglutination Inhibition (HI) Antibody Titers
Description	Number of patients and percentage of subjects achieving hemagglutination inhibition (HI) titer≥40
Time Frame	Week 1, 4, and 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SD-IIV3	HD-IIV3
Arm/Group Description	Standard dose flu vaccine	high dose flu vaccine
Measure Participants	30	32
week 1	14 46.7%	19 59.4%
Week 4	16 53.3%	23 71.9%
Week 12	15 50%	21 65.6%

3. Secondary Outcome

Title	All Cause ED Visits/Unscheduled Clinic Visits
Description	All-cause outpatient/Emergency department visits during study follow-up (other than pre-specified post transplant follow-up visits).
Time Frame	day 1 - 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High Dose Flu Vaccine (HD-IIV3)	Standard Dose (SD-IIV3)
Arm/Group Description	influenza trivalent inactive vaccine high dose. IM (intramuscular) injection one time administration influenza trivalent inactive vaccine high dose: one time IM injection of high dose influenza vaccine to measure immunogenicity, safety, and efficacy in organ transplant recipients	influenza trivalent inactive vaccine IM injection one time administration influenza trivalent inactive vaccine: one time IM injection of standard influenza vaccine to measure immunogenicity, safety, and efficacy in organ transplant recipients
Measure Participants	32	30
Count of Participants [Participants]	30 100%	25 78.1%

4. Secondary Outcome

Title	Number and Percentage of Subjects in Each Group Achieving Seroconversion for Each Strain
Description	Number and percentage of subjects in each group achieving seroconversion (at least 4-fold increase in titers from baseline) for each any strain at weeks 4 and 12
Time Frame	Week 4 and Week 12

Outcome Measure Data

Analysis Population Description

Analysis performed only for participants between ages of 18 and 65.

Arm/Group Title	Standard Dose Flu Vaccine	High Dose Flu Vaccine
Arm/Group Description	standard influenza trivalent inactive vaccine dose. IM (intramuscular) injection one time administration	influenza trivalent inactive vaccine IM injection one time administration
Measure Participants	27	26
week 4	7 23.3%	6 18.8%
week 12	7 23.3%	7 21.9%

Adverse Events

Arm/Group Title	SD-IIV3		HD-IIV3
Arm/Group Description	The safety and immunogenicity of seasonal influenza vaccination using Standard-dose trivalent (SD-IIV3) in recipients of solid organ transplants who were at least 30 days after transplantation via a randomized blinded study.		The safety and immunogenicity of seasonal influenza vaccination using high-dose trivalent (HD-IIV3) in recipients of solid organ transplants who were at least 30 days after transplantation via a randomized blinded study.
All Cause Mortality
	SD-IIV3		HD-IIV3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/32 (0%)
Serious Adverse Events
	SD-IIV3		HD-IIV3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/32 (0%)
Other (Not Including Serious) Adverse Events
	SD-IIV3		HD-IIV3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/30 (43.3%)		14/32 (43.8%)
General disorders
redness	8/30 (26.7%)		12/32 (37.5%)
swelling	13/30 (43.3%)		14/32 (43.8%)
fever	10/30 (33.3%)		10/32 (31.3%)
headache	9/30 (30%)		9/32 (28.1%)
fatigue	7/30 (23.3%)		11/32 (34.4%)
nausea, vomiting, diarrhea	5/30 (16.7%)		9/32 (28.1%)
myalgia	10/30 (33.3%)		9/32 (28.1%)
arthralgia	10/30 (33.3%)		8/32 (25%)
Musculoskeletal and connective tissue disorders
local pain	13/30 (43.3%)		13/32 (40.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.